It has been demonstrated that cytotoxic T lymphocytes (CTLs) recognize epitope peptides derived from tumor-associated antigens (TAAs) found on major the histocompatibility complex (MHC) class I molecule, and then kill the tumor cells. Since the discovery of melanoma antigen (MAGE) family as the first example of TAAs, many other TAAs have been discovered through immunological approaches (NPL 1, Boon T, Int J Cancer 1993 May 8, 54(2): 177-80; NPL 2, Boon T & van der Bruggen P, J Exp Med 1996 Mar. 1, 183(3): 725-9). Some of these TAAs are currently undergoing clinical development as immunotherapeutic targets.
Favorable TAAs are indispensable for the proliferation and survival of cancer cells. The use of such TAAs as targets for immunotherapy may minimize the well-described risk of immune escape of cancer cells attributable to deletion, mutation, or down-regulation of TAAs as a consequence of therapeutically driven immune selection. Accordingly, the identification of new TAAs capable of inducing potent and specific anti-tumor immune responses, warrants further development; accordingly, the clinical application of peptide vaccination strategies for various types of cancer is ongoing (NPL 3, Harris C C, J Natl Cancer Inst 1996 Oct. 16, 88(20): 1442-55; NPL 4, Butterfield L H et al., Cancer Res 1999 Jul. 1, 59(13): 3134-42; NPL 5, Vissers J L et al., Cancer Res 1999 Nov. 1, 59(21): 5554-9; NPL 6, van der Burg S H et al., J Immunol 1996 May 1, 156(9): 3308-14; NPL 7, Tanaka F et al., Cancer Res 1997 Oct. 15, 57(20): 4465-8; NPL 8, Fujie T et al., Int J Cancer 1999 Jan. 18, 80(2): 169-72; NPL 9, Kikuchi M et al., Int J Cancer 1999 May 5, 81(3): 459-66; NPL 10, Oiso M et al., Int J Cancer 1999 May 5, 81(3): 387-94). To date, several clinical trials using these tumor-associated antigen derived peptides have been reported. Unfortunately, many of the current cancer vaccine trial have shown only a low objective response rate (NPL 11, Belli F et al., J Clin Oncol 2002 Oct. 15, 20(20): 4169-80; NPL 12, Coulie P G et al., Immunol Rev 2002 October, 188: 33-42; NPL 13, Rosenberg S A et al., Nat Med 2004 September, 10(9): 909-15). Accordingly, there remains a need for new TAAs as immunotherapeutic targets.
SEMA5B is a member of the semaphorin protein family, a family of proteins that play an important role in axonal guidance during neural development (NPL 14, O'Connor T P et. al., Neural Dev. 2009 May 23; 4:18). Recent studies suggest that the functions of semaphorin family protein relate not only to nervous system but to organogenesis, angiogenesis and a development of cancer.
In the course of gene-expression profile analyses using a cDNA microarray consisting of 23,040 genes as a means to clarify the molecular mechanism of renal cell carcinoma (RCC), SEMA5B was found to be frequently up-regulated in RCC. Subsequent Northern blot analysis reveals that SEMA5B transcript is highly expressed in RCC tissues but barely detectable in normal human tissues except fetal brain and fetal kidney. Furthermore, knockdowns of SEMA5B by siRNA in RCC cell lines have been shown to attenuate the growth of RCC cells (NPL15, Hirota E. et. al., Int J. Oncol. 2006 October; 29(4):799-827; PTL1, WO2007/013575).